Lifelong longitudinal assessment of the contribution of multi-fractal fluctuations to heart rate and heart rate variability in aging mice: role of the sinoatrial node and autonomic nervous system.

Aging is a major risk factor for sinoatrial node (SAN) dysfunction, which can impair heart rate (HR) control and heart rate variability (HRV). HR and HRV are determined by intrinsic SAN function and its regulation by the autonomic nervous system (ANS). The purpose of this study was to use multi-scale multi-fractal detrended fluctuation analysis (MSMFDFA; a complexity-based approach to analyze multi-fractal dynamics) to longitudinally assess changes in multi-fractal HRV properties and SAN function in ECG time series recorded repeatedly across the full adult lifespan in mice.

Evaluation of non-linear heart rate variability using multi-scale multi-fractal detrended fluctuation analysis in mice: Roles of the autonomic nervous system and sinoatrial node.

Nonlinear analyses of heart rate variability (HRV) can be used to quantify the unpredictability, fractal properties and complexity of heart rate. Fractality and its analysis provides valuable information about cardiovascular health. Multi-Scale Multi-Fractal Detrended Fluctuation Analysis (MSMFDFA) is a complexity-based algorithm that can be used to quantify the multi-fractal dynamics of the HRV time series through investigating characteristic exponents at different time scales.

Loss of Natriuretic Peptide Receptor C Enhances Sinoatrial Node Dysfunction in Aging and Frail Mice.

Heart rate (HR) is controlled by the sinoatrial node (SAN). SAN dysfunction is highly prevalent in aging; however, not all individuals age at the same rate. Rather, health status during aging is affected by frailty.

Atrial Fibrillation in Aging and Frail Mice: Modulation by Natriuretic Peptide Receptor C.

[Figure: see text].

Impacts of frailty on heart rate variability in aging mice: Roles of the autonomic nervous system and sinoatrial node.

Background: Heart rate variability (HRV) is determined by intrinsic sinoatrial node (SAN) activity and the autonomic nervous system (ANS). HRV is reduced in aging; however, aging is heterogeneous. Frailty, which can be measured using a frailty index (FI), can quantify health status in aging separately from chronological age.

Electrical and structural remodeling contribute to atrial fibrillation in type 2 diabetic db/db mice.

Background: Atrial fibrillation (AF) is highly prevalent in diabetes mellitus (DM), yet the basis for this finding is poorly understood. Type 2 DM may be associated with unique patterns of atrial electrical and structural remodeling; however, this has not been investigated in detail.

Objective: The purpose of this study was to investigate AF susceptibility and atrial electrical and structural remodeling in type 2 diabetic db/db mice.

Altered heart rate variability in angiotensin II-mediated hypertension is associated with impaired autonomic nervous system signaling and intrinsic sinoatrial node dysfunction.

Background: Hypertensive heart disease is associated with sinoatrial node (SAN) dysfunction and reductions in heart rate variability (HRV). Alterations in HRV could occur in association with changes in autonomic nervous system (ANS) activity, changes in SAN function and responsiveness to ANS agonists, or both. These relationships are unclear.

Loss of insulin signaling may contribute to atrial fibrillation and atrial electrical remodeling in type 1 diabetes.

Atrial fibrillation (AF) is prevalent in diabetes mellitus (DM); however, the basis for this is unknown. This study investigated AF susceptibility and atrial electrophysiology in type 1 diabetic Akita mice using in vivo intracardiac electrophysiology, high-resolution optical mapping in atrial preparations, and patch clamping in isolated atrial myocytes. qPCR and western blotting were used to assess ion channel expression.

Morphogenetic control of zebrafish cardiac looping by Bmp signaling.

Cardiac looping is an essential and highly conserved morphogenetic process that places the different regions of the developing vertebrate heart tube into proximity of their final topographical positions. High-resolution 4D live imaging of mosaically labelled cardiomyocytes reveals distinct cardiomyocyte behaviors that contribute to the deformation of the entire heart tube. Cardiomyocytes acquire a conical cell shape, which is most pronounced at the superior wall of the atrioventricular canal and contributes to S-shaped bending.

NPR-C (Natriuretic Peptide Receptor-C) Modulates the Progression of Angiotensin II-Mediated Atrial Fibrillation and Atrial Remodeling in Mice.

Background: Atrial fibrillation (AF) commonly occurs in hypertension and in association with elevated Ang II (angiotensin II) levels. The specific mechanisms underlying Ang II-mediated AF are unclear, and interventions to prevent the effects of Ang II are lacking. NPs (natriuretic peptides), which elicit their effects through specific NP receptors, including NPR-C (natriuretic peptide receptor-C), are cardioprotective hormones that affect cardiac structure and function.

Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice.

Sinoatrial node (SAN) disease mechanisms are poorly understood, and therapeutic options are limited. Natriuretic peptide(s) (NP) are cardioprotective hormones whose effects can be mediated partly by the NP receptor C (NPR-C). We investigated the role of NPR-C in angiotensin II (Ang II)-mediated SAN disease in mice.

Distinct patterns of atrial electrical and structural remodeling in angiotensin II mediated atrial fibrillation.

Atrial fibrillation (AF) is prevalent in hypertension and elevated angiotensin II (Ang II); however, the mechanisms by which Ang II leads to AF are poorly understood. Here, we investigated the basis for this in mice treated with Ang II or saline for 3 weeks. Ang II treatment increased susceptibility to AF compared to saline controls in association with increases in P wave duration and atrial effective refractory period, as well as reductions in right and left atrial conduction velocity.

Altered heart rate regulation by the autonomic nervous system in mice lacking natriuretic peptide receptor C (NPR-C).

Natriuretic peptides (NPs) play essential roles in the regulation of cardiovascular function. NP effects are mediated by receptors known as NPR-A, NPR-B or NPR-C. NPs have potent effects on regulation of heart rate (HR) by the autonomic nervous system (ANS), but the role of NPR-C in these effects has not been investigated.

Atrial structure, function and arrhythmogenesis in aged and frail mice.

Atrial fibrillation (AF) is prevalent in aging populations; however not all individuals age at the same rate. Instead, individuals of the same chronological age can vary in health status from fit to frail. Our objective was to determine the impacts of age and frailty on atrial function and arrhythmogenesis in mice using a frailty index (FI).

The impacts of age and frailty on heart rate and sinoatrial node function.

Key Points: Sinoatrial node (SAN) function declines with age; however, not all individuals age at the same rate and health status can vary from fit to frail. Frailty was quantified in young and aged mice using a non-invasive frailty index so that the impacts of age and frailty on heart rate and SAN function could be assessed. SAN function was impaired in aged mice due to alterations in electrical conduction, changes in SAN action potential morphology and fibrosis in the SAN.

Electrophysiological effects of natriuretic peptides in the heart are mediated by multiple receptor subtypes.

Natriuretic peptides (NPs) are a family of cardioprotective hormones with numerous beneficial effects in cardiovascular system. The NP family includes several peptides including atrial NP (ANP), B-type NP (BNP), C-type NP (CNP) and Dendroaspis NP (DNP). These peptides elicit their effects by binding to three distinct cell surface receptors called natriuretic peptide receptors A, B and C (NPR-A, NPR-B and NPR-C).

Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis.

Background: Atrial natriuretic peptide (ANP) is a hormone with numerous beneficial cardiovascular effects. Recently, a mutation in the ANP gene, which results in the generation of a mutant form of ANP (mANP), was identified and shown to cause atrial fibrillation in people. The mechanism(s) through which mANP causes atrial fibrillation is unknown.

Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice.

Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that impairs autonomic regulation of heart rate (HR). This has been attributed to damage to the nerves that modulate spontaneous pacemaker activity in the sinoatrial node (SAN). Our objective was to test the hypothesis that impaired parasympathetic regulation of HR in diabetes is due to reduced responsiveness of the SAN to parasympathetic agonists.

Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C.

Natriuretic peptides (NPs) are critical regulators of the cardiovascular system that are currently viewed as possible therapeutic targets for the treatment of heart disease. Recent work demonstrates potent NP effects on cardiac electrophysiology, including in the sinoatrial node (SAN) and atria. NPs elicit their effects via three NP receptors (NPR-A, NPR-B and NPR-C).

Predicting the risk of squamous dysplasia and esophageal squamous cell carcinoma using minimum classification error method.

Early detection of squamous dysplasia and esophageal squamous cell carcinoma is of great importance. Adopting computer aided algorithms in predicting cancer risk using its risk factors can serve in limiting the clinical screenings to people with higher risks. In the present study, we show that the application of an advanced classification method, the Minimum Classification Error, could considerably enhance the classification performance in comparison to the logistic regression model and the variable structure fuzzy neural network, as the latest successful methods.

Periodic and chaotic dynamics in a map-based model of tumor-immune interaction.

Clinicians and oncologists believe that tumor growth has unpredictable dynamics. For this reason they encounter many difficulties in the treatment of cancer. Mathematical modeling is a great tool to improve our better understanding of the complicated biological system of tumor growth.

A variable structure fuzzy neural network model of squamous dysplasia and esophageal squamous cell carcinoma based on a global chaotic optimization algorithm.

Identification of squamous dysplasia and esophageal squamous cell carcinoma (ESCC) is of great importance in prevention of cancer incidence. Computer aided algorithms can be very useful for identification of people with higher risks of squamous dysplasia, and ESCC. Such method can limit the clinical screenings to people with higher risks.